Iron deficiency remains the most common form of malnutrition worldwide, increasing the risk of disability and death among more than two billion people. Lack of iron causes anemia, decreases physical capabilities, impairs cognitive and behavioral development, compromises immune responsiveness and when severe, increases mortality during infancy and childhood. Iron supplements are needed for prevention of iron deficiency in those with increased iron requirements, especially infants, children and women of childbearing age, and for correction of iron deficiency anemia in all affected individuals.
However, in areas with endemic malaria, untargeted iron supplementation is no longer recommended as a means of providing additional iron because an increased risk of hospitalization and death was found in a trial of universal iron and folic acid supplementation for preschool children in Pemba, Tanzania. Using an elevated eZnPP/heme molar ratio (>80 μmol/mol heme) as the criterion for iron deficiency, iron-deficient children were found to benefit from supplementation. Their risk of severe illness and death decreased by 38%. In contrast, iron-replete children were harmed by supplementation. In fact, their risk of severe illness and death increased by 63% after iron supplementation. See, e.g., Sazawal S. et al., Effects of routine prophylactic supplementation with iron and folic acid on admission to hospital and mortality in preschool children in a high malaria transmission setting: community-based, randomised, placebo-controlled trial. Lancet 2006; 367: 133-143. In view of this risk, a World Health Organization (WHO) Consultation recommended that, in malaria-endemic areas, (i) iron supplements should be given to children only after screening for iron deficiency and (ii) the measurement of eZnPP was the preferred indicator for identifying iron-deficient children who could benefit from iron supplementation. See, WHO Conclusions and recommendations of the WHO Consultation on prevention and control of iron deficiency in infants and young children in malaria-endemic areas. Food Nutr Bull 2007; 28: S621-7.
In resource-limited settings, like those in regions with endemic malaria, the use of the existing front-face hematofluorometer technique for measurement of eZnPP is constrained by the requirement for a blood sample obtained by finger- or venipuncture, the necessity for a trained technician for operation, use of an electrical power supply, a need for frequent recalibration and expense. Other currently available means of assessing iron status also require blood samples and even more complex and costly laboratory facilities and processing. Because of the lack of means to determine iron status, the effective result of the WHO recommendation has been the cessation of programs of iron supplementation in almost all malarial areas.
Thus, there is a need for a new technique that overcomes the technical difficulties of existing invasive techniques for identifying those individuals in malarial areas who would benefit from iron supplementation to permit safe and effective prevention and correction of iron deficiency, while avoiding harm to those who are iron replete.
Globally, 30% to 70% of the populations in developing countries are iron deficient, with the highest prevalence among persons who have diets low in bio-available iron. In developed countries, despite increased amounts of dietary bio-available iron, iron nutrition nevertheless remains a problem in subpopulations with the highest iron requirements, especially among infants, children and women of childbearing age. Without iron supplementation, most women will become iron deficient during pregnancy. Thus, screening for iron deficiency is a crucial component of healthcare. Initially, iron deficiency may be asymptomatic or produce only nonspecific manifestations, such as weakness and easy fatigability. As iron deficiency becomes more severe, anemia develops and progressively restricts work capacity and tolerance of physical exertion. Early detection of iron deficiency permits prompt recognition and management of underlying causes. Most commonly, a diet with inadequate amounts of bio-available iron is responsible. In these individuals, iron deficiency may be corrected by nutritional approaches, such as consuming iron-rich food as well as food which helps the body absorb iron more effectively, such as food high in vitamin C, or by iron supplementation.
Thus, there is also a need for periodic iron monitoring in a safe, effective manner without the need for a blood sample. There is also a need to provide a technique and apparatus that can be used as a point-of-care screening device for iron deficiency in pediatric, obstetric and medical facilities, and in blood donation centers worldwide, and by individuals to monitor their own iron status in their homes or portably, without the need to be in a clinical setting. Because eZnPP is also elevated in lead poisoning, a noninvasive method would be useful for screening those people at risk from occupational or environmental exposure.
There is also a need to provide a technique and apparatus for measuring the concentration of an analyte in the blood of a patient. For example, in certain settings—such as a hospital or clinical environment with access to sterile conditions and adequate equipment—it is acceptable and/or desirable to analyze iron levels in the blood. A technique and apparatus which provides greater accuracy and consistency when compared with existing techniques is needed.